Hallucinogens

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Transcript of Hallucinogens

Hallucinogens I suddenly became strangely inebriated. The external world became changed as in a dream. Objects appeared to gain inrelief;they assumed unusual dimensions; and colors became more glowing. Even self-perception and the sense of time were changed. When the eyes were closed, colored pictures flashed past in a quickly changing kaleidoscope. After a few hours, the not unpleasant inebriation,which had been experienced whilst I was fully conscious, disappeared. What had caused this condition?-Laboratory Notes 1943 Albert Hofmann objectives 1 2 3 Understanding the mechanisms:Receptors, pathways, neurotransmitters, and brain regions Apply that knowledge to understanding the subjective and somatic effects Determine the safety and raise awareness about the scientific and therapeutic uses Case what do we know/need to know? brain regionsreceptorsneurotransmitters Classes of hallucinogens Encompasses all drugs that alter psyche and promote altered states of consciousness“Classic psychedelics” are serotonergic hallucinogens Phenethylamines TryptaminesErgolines (LSD) Lysergic acid diethylamide(LSD) Serotonin DMT Psilocin Mescaline Model Pharmacology Animal Models Dosage and Metabolism Pharmacological Facts Physical effects Drug Discrimination Introduction Animal trained to emit a response initiated by administration of training drug -Appetitive reinforcement or shock avoidanceAnimals trained to recognize stimulus effects of training drug vs. control/salineDifferent doses of training drug or drug with similar mechanisms can help to develop dose/response curve Drug elicited headtwitch response (HTR) Rapid, rational jerking of the head which is different than grooming or scratching behaviorsSelective behavioral model for 5-HT2a receptor agonist activity in rodents-Can develop dose-effect curveDirect and indirect 5-HT agonists induce this effectAntagonists block this effect Self-administration Animal trained to perform a task when it wants the drugOral, subcutaneous, intravenous catheterUsed to study reinforcing effectsDOM(mescaline analog) was not able to maintain self-administration in rhesus monkeysMDMA (ecstasy) is a phenethylamine that was able to maintain self-administration in baboons and mice LSD Minimal recognizable = 25-75 uμg p.o.Moderate dose = (75–-100 μug p.o.)“Optimum” dose = 100–-200 uμgClinical dose = 100 μugCommon recreational dosage rarely cause frank hallucinationAcute psychological effects last b/w 6 to 10 hoursHalf life in humans is 175 minutes Phenethylamines low nanomolar affinities for 5-HT2a receptors and 1000-fold higher affinity for 1a receptors10 fold increase in affinity for 2a over 2cAll types of hallucinogens are partial agonists at 2c receptorIncreased receptor density leads to increased HTRRapid development of tolerance with repeated administrationDownregulation of 2a receptorsBehaviors mediated by 2c receptors are unaltered with increased administration; 2c receptor density also did not changeAffinity for 2a receptor comparable to that of LSDOrder of potency = 5-HT2A > 5-HT2B > 5-HT2C